Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents

Phase 1

• Conditions: Non-malignant Disease; Haploidentical Hematopoietic Stem Cell Transplantation; Malignant Disease
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: anti-thymocyte globulin; Biological: filgrastim; Radiation: Total body irradiation; Procedure: TCRαβ-depleted hematopoietic cell transplantation; Device: CliniMACS

• Registration Number: NCT02014506
• Lead Sponsor: Asan Medical Center

Brief Summary

Purpose of study: This phase I/II trial is to evaluate the safety and feasibility of TCRαβ-depleted graft from haploidentical family donors in treating children and adolescents with malignant or non-malignant diseases.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-12-04
• Study First Submitted QC: 2013-12-12
• Study First Posted: 2013-12-18
• Study Start: 2017-01
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-24
• Last Update Posted: 2017-03-28
• Primary Completion: 2018-12
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

A. Disease inclusions

1. Hematologic malignancy:

   • Acute lymphoblastic leukemia including induction failure, CR1 (Ph+, t(4:11), hypodiploid and other very high risk features), ≥ CR2, infant ALL with MLL or other unfavorable features
   • Acute myeloid leukemia excluding CR1 with t(8:21), inv(16), t(15:17), and Down syndrome
   • Myelodysplastic syndrome: RCC with -7 or RCC in need of transfusion
   • Chronic myeloid leukemia in AP
   • Juvenile myelomonocytic leukemia
   • Malignant lymphoma, NHL or HD, after failed autologous HSCT
   • Other

2. Non-hematologic malignancy

   • Relapsed or refractory solid tumors including neuroblastoma, rhabdomyosarcoma and so on

3. Non-malignant hematologic disease

   • Acquired severe and very severe aplastic anemia
   • Fanconi anemia
   • Paroxysmal nocturnal hemoglobinuria
   • Congenital dyserythropoietic anemia
   • Others

4. Inherited or metabolic disease

   • Hemophagocytic lymphohistiocytosis
   • Malignant osteopetrosis
   • Storage diseases
   • Others B. Recipient inclusions

5. Age < 21 years 2. No HLA-identical stem cell donor available 3. Lansky-Play performance score >60 4. No active infection at the time of transplantation

Exclusion Criteria

1. HIV-infection
2. Presence of active and serious infection
3. Cardiac ejection fraction <35% on echocardiography
4. Severe pulmonary dysfunction (DLCO <30%)
5. Liver function abnormalities with bilirubin >4mg/dL and elevation of transaminases > 400U/L
6. Concurrent severe or uncontrolled medical disease
7. Patients who are pregnant
8. Patients unwilling or unable to comply with the protocol or unable to give informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HAPLO	anti-thymocyte globulin	-
HAPLO	filgrastim	-
HAPLO	Total body irradiation	-
HAPLO	TCRαβ-depleted hematopoietic cell transplantation	-
HAPLO	CliniMACS	-
HAPLO	Fludarabine	-
HAPLO	Cyclophosphamide	-

Primary Outcome Measures

Name	Time	Method
To evaluate tralsplant-related mortality after haploidentical hematopoietic stem cell transplantation using TCRαβ-depleted graft	1 year posttransplant

Secondary Outcome Measures

Name	Time	Method
To estimate the reactivation rate of CMV, EBV	100 days and 1 year posttransplant
To estimate the incidence of relapse	100 days and 1 year post-transplant
To estimate the incidence and severity of chronic GVHD	1 year posttransplant
To estimate the incidence of bacterial, fungal and viral infection	100 days and 1 year posttransplant
To evaluate the immune reconstitution of T, B, and NK cells	days 7, 14, 21, 28, 60, 90, 180, 270, and 365 days post-transplant
To evaluate the lineage-specific chimerism using flow cytomery of CD3+, CD19, CD56, TCR αβ, and TCRγδ at pre-transplant	days 7, 10, 14, 21, 28, 60, 90, 180, 270 and 365 post-transplant
To assess event free survival	1 year posttransplant
To assess engraftment and graft failure	28 days posttransplant
To estimate the risk of acute GVHD	100 days posttransplant
To estimate the overall survival	1 year posttransplant

Trial Locations

Locations (1)

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of